title: Modifications of hippocampal circuits and early disruption of adult neurogenesis in the tg2576 mouse model of Alzheimer's disease.
abstract: At advanced stages of Alzheimer's disease, cognitive dysfunction is accompanied by severe alterations of hippocampal circuits that may largely underlie memory impairments. However, it is likely that anatomical remodeling in the hippocampus may start long before any cognitive alteration is detected. Using the well-described Tg2576 mouse model of Alzheimer's disease that develops progressive age-dependent amyloidosis and cognitive deficits, we examined whether specific stages of the disease were associated with the expression of anatomical markers of hippocampal dysfunction. We found that these mice develop a complex pattern of changes in their dentate gyrus with aging. Those include aberrant expression of neuropeptide Y and reduced levels of calbindin, reflecting a profound remodeling of inhibitory and excitatory circuits in the dentate gyrus. Preceding these changes, we identified severe alterations of adult hippocampal neurogenesis in Tg2576 mice. We gathered converging data in Tg2576 mice at young age, indicating impaired maturation of new neurons that may compromise their functional integration into hippocampal circuits. Thus, disruption of adult hippocampal neurogenesis occurred before network remodeling in this mouse model and therefore may account as an early event in the etiology of Alzheimer's pathology. Ultimately, both events may constitute key components of hippocampal dysfunction and associated cognitive deficits occurring in Alzheimer's disease.
authors.affiliation: Université de Toulouse (UPS) Centre de Recherches sur la Cognition Animale, Toulouse, France ; Centre National de la Recherche Scientifique (CNRS) Centre de Recherches sur la Cognition Animale, Toulouse, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Krezymon
authors.forename: Kevin
authors.initials: K
authors.lastname: Richetin
authors.forename: Hélène
authors.initials: H
authors.lastname: Halley
authors.forename: Laurent
authors.initials: L
authors.lastname: Roybon
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Lassalle
authors.forename: Bernard
authors.initials: B
authors.lastname: Francès
authors.forename: Laure
authors.initials: L
authors.lastname: Verret
authors.forename: Claire
authors.initials: C
authors.lastname: Rampon
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D064092:Calbindin 1 / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D064092:Calbindin 1; D009478:Neuropeptide Y